Liposomes were first published by British hematologist Dr Alec D Bangham FRS in 1965, at the Babraham Institute, in Cambridge. Structurally, liposomes are holy spheres made of lipids, and have a diameter of approximately 0.025˜3.5 μm, so that they can be immiscibly dispensed in aqueous phase. Lipid membranes of liposomes are present as bilayers and mainly composed of phospholipids. The phospholipids have a head group and a tail group. The head is attracted to water, and the tail, which is made of a long hydrocarbon chain, exactly like an erythrocyte membrane or cell membrane. Due to their bilayer structures, liposomes can be used to encapsulate both hydrophilic molecules (and ionic agent) and hydrophobic compounds, and thus can be used to be carriers for drug delivery. While being used for drug delivery, liposomes have various functions. For example, liposomes are suitable for encapsulating hydrophilic/ionic and hydrophobic drugs, and additionally have characteristics such as biocompatibility and biodegradability. They are capable of protecting drugs passing through metabolic systems to the target location of a human body. Liposomes also have the ability for lysis and release control, are suitable for being carriers for hydrophobic and hydrophilic agents. Thus, liposomes have great potential to apply in the fields of biomedicine, nanotechnology, bioanalysis or artificial cell membrane system.
The methods for preparation of liposomes include thin-film hydration method, ethanol injection method, reverse-phase evaporation method and double emulsion method, wherein the double emulsion method is highly related with the present invention.
With reference to FIG. 1(A)-1(E), which depict the conventional double emulsion method for preparation of liposomes. The process is simply described as follow. Firstly, high concentration lipids are dissolved in an organic solvent (FIG. 1A), and an aqueous solution is added and thus to be stably dispersed in the organic solvent to form an emulsion (FIG. 1B, 1C). Then the emulsion is added to water to form a water-in-oil-in-water double emulsion (W/O/W double emulsion) (FIG. 1D). Finally, the organic solvent is evaporated by a rotary evaporator or by placing for a while, so as to obtain bilayer liposomes (FIG. 1E). The liposome size is determined by the initial formed droplet size (emulsion). Although the double emulsion method may need a delicate microfluidic system, it has high encapsulation efficiency.
However, the traditional method for liposome production has many drawbacks. For example, encapsulation efficiency is too low. Additionally, the process for producing liposomes usually needs sonicators or microfluidic systems. Unfortunately, sonicators may lower the encapsulation efficiency, and microfluidic systems are merely able to produce micro-size liposomes. And the traditional methods are incapable of realizing programmable mass production.